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Adoptive cellular immunotherapy to the endometrial carcinoma cell line xenografts in nude mice
H Shimizu1, M Inoue, O Tanizawa
1Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
Abstract:
The present study was designed to examine the immunotherapeutic properties of lymphokine-activated killer (LAK) cells against uterine endometrial cancers. Three endometrial cancer cell lines, ISHIKAWA, SNG-M, and HHUA, were shown to be specifically lysed in short-term 51Cr-release assay, although the susceptibility was different among the cell lines. The xenograft tumors of ISHIKAWA and SNG-M exhibited high susceptibility to LAK cells in the in vitro assay and responded well to the adoptive transfer of LAK cells in nude mice. On the other hand, the xenograft of HHUA showed low reactivity to LAK cells and showed no response to the adoptive immunotherapy. However, the adoptive transfer of LAK cells combined with intraperitoneal administration of both recombinant interleukin-2 (rIL-2) and lentinan markedly inhibited the growth of HHUA xenografts in nude mice, while no response was observed in nude mice treated with LAK cells plus either rIL-2 or lentinan, or treated with rIL-2 plus lentinan alone. These results suggest the clinical application of adoptive immunotherapy in association with LAK cells, rIL-2, and lentinan as a treatment of gynecologic cancers.
Insights
Adoptive immunotherapy using lymphokine-activated killer (LAK) cells shows promise for uterine endometrial cancers. Combining LAK cells with recombinant interleukin-2 (rIL-2) and lentinan effectively inhibited tumor growth in mice.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Uterine endometrial cancers are a significant health concern.
- Current immunotherapies have limitations in treating these cancers.
Purpose of the Study:
- To investigate the efficacy of lymphokine-activated killer (LAK) cells as an immunotherapeutic approach against endometrial cancer.
- To evaluate the synergistic effects of LAK cells combined with recombinant interleukin-2 (rIL-2) and lentinan.
Main Methods:
- In vitro assessment of LAK cell-mediated lysis of endometrial cancer cell lines (ISHIKAWA, SNG-M, HHUA) using 51Cr-release assay.
- In vivo evaluation of LAK cell adoptive transfer efficacy in nude mouse xenograft models of endometrial cancer.
- Combination therapy assessment involving LAK cells, rIL-2, and lentinan.
Main Results:
- LAK cells demonstrated specific lysis against ISHIKAWA, SNG-M, and HHUA cell lines in vitro, with varying susceptibility.
- Adoptive transfer of LAK cells effectively inhibited growth of ISHIKAWA and SNG-M xenografts in nude mice.
- Combination therapy of LAK cells with rIL-2 and lentinan significantly inhibited HHUA xenograft growth, unlike monotherapies.
Conclusions:
- LAK cell-based immunotherapy holds potential for treating uterine endometrial cancers.
- The combination of LAK cells, rIL-2, and lentinan offers a potent therapeutic strategy for resistant endometrial cancer xenografts.
- This combined approach warrants further investigation for clinical application in gynecologic cancers.